tbuckley/cabot-search huggingface dataset:
Universal health coverage in China part 2: addressing challenges and recommendations
Authors: Winnie Yip, Hongqiao Fu, Weiyan Jian, Jue Liu, Jay Pan, Duo Xu, Hanmo Yang, Tiemin Zhai
Journal: The Lancet Public Health (2023)

This report analyses the underlying causes of China's achievements and gaps in universal health coverage over the past 2 decades and proposes policy recommendations for advancing universal health coverage by 2030. Although strong political commitment and targeted financial investment have produced positive outcomes in reproductive, maternal, newborn, and child health and infectious diseases, a fragmented and hospital-centric delivery system, rising health-care costs, shallow benefit coverage of health insurance schemes, and little integration of health in all policies have restricted China's ability to effectively prevent and control chronic disease and provide adequate financial risk protection, especially for lower-income households. Here, we used a health system conceptual framework and we propose a set of feasible policy recommendations that draw from international experiences and first-hand knowledge of China's unique institutional landscape. Our six recommendations are: instituting a primary care-focused integrated delivery system that restructures provider incentives and accountability mechanisms to prioritise prevention; leveraging digital tools to support health behaviour change; modernising information campaigns; improving financial protection through insurance reforms; promoting a health in all policy; and developing a domestic monitoring framework with refined tracer indicators that reflects China's disease burden.
Historic Museum Samples Provide Evidence for a Recent Replacement of <i>Wolbachia</i> Types in European <i>Drosophila melanogaster</i>
Authors: Anton Strunov, Sandra Kirchner, Julia Schindelar, Luise Kruckenhauser, Elisabeth Haring, Martin Kapun
Journal: Molecular Biology and Evolution (2023)

Abstract Wolbachia is one of the most common bacterial endosymbionts, which is frequently found in numerous arthropods and nematode taxa. Wolbachia infections can have a strong influence on the evolutionary dynamics of their hosts since these bacteria are reproductive manipulators that affect the fitness and life history of their host species for their own benefit. Host–symbiont interactions with Wolbachia are perhaps best studied in the model organism Drosophila melanogaster, which is naturally infected with at least 5 different variants among which wMel and wMelCS are the most frequent ones. Comparisons of infection types between natural flies and long-term lab stocks have previously indicated that wMelCS represents the ancestral type, which was only very recently replaced by the nowadays dominant wMel in most natural populations. In this study, we took advantage of recently sequenced museum specimens of D. melanogaster that have been collected 90 to 200 yr ago in Northern Europe to test this hypothesis. Our comparison to contemporary Wolbachia samples provides compelling support for the replacement hypothesis. Our analyses show that sequencing data from historic museum specimens and their bycatch are an emerging and unprecedented resource to address fundamental questions about evolutionary dynamics in host–symbiont interactions. However, we also identified contamination with DNA from crickets that resulted in co-contamination with cricket-specific Wolbachia in several samples. These results underpin the need for rigorous quality assessments of museomic data sets to account for contamination as a source of error that may strongly influence biological interpretations if it remains undetected.
Genetic Load and Adaptive Potential of a Recovered Avian Species that Narrowly Avoided Extinction
Authors: Georgette Femerling, Cock van Oosterhout, Shaohong Feng, Rachel M Bristol, Guojie Zhang, Jim Groombridge, M Thomas P. Gilbert, Hernán E Morales
Journal: Molecular Biology and Evolution (2023)

Abstract High genetic diversity is a good predictor of long-term population viability, yet some species persevere despite having low genetic diversity. Here we study the genomic erosion of the Seychelles paradise flycatcher (Terpsiphone corvina), a species that narrowly avoided extinction after having declined to 28 individuals in the 1960s. The species recovered unassisted to over 250 individuals in the 1990s and was downlisted from Critically Endangered to Vulnerable in the International Union for the Conservation of Nature Red List in 2020. By comparing historical, prebottleneck (130+ years old) and modern genomes, we uncovered a 10-fold loss of genetic diversity. Highly deleterious mutations were partly purged during the bottleneck, but mildly deleterious mutations accumulated. The genome shows signs of historical inbreeding during the bottleneck in the 1960s, but low levels of recent inbreeding after demographic recovery. Computer simulations suggest that the species long-term small Ne reduced the masked genetic load and made the species more resilient to inbreeding and extinction. However, the reduction in genetic diversity due to the chronically small Ne and the severe bottleneck is likely to have reduced the species adaptive potential to face environmental change, which together with a higher load, compromises its long-term population viability. Thus, small ancestral Ne offers short-term bottleneck resilience but hampers long-term adaptability to environmental shifts. In light of rapid global rates of population decline, our work shows that species can continue to suffer the effect of their decline even after recovery, highlighting the importance of considering genomic erosion and computer modeling in conservation assessments.
Inference of Admixture Origins in Indigenous African Cattle
Authors: Kwondo Kim, Donghee Kim, Olivier Hanotte, Charles Lee, Heebal Kim, Choongwon Jeong
Journal: Molecular Biology and Evolution (2023)

Present-day African cattle retain a unique genetic profile composed of a mixture of the Bos taurus and Bos indicus populations introduced into the continent at different time periods. However, details of the admixture history and the exact origins of the source populations remain obscure. Here, we infer the source of admixture in the earliest domestic cattle in Africa, African taurine. We detect a significant contribution (up to ∼20%) from a basal taurine lineage, which might represent the now-extinct African aurochs. In addition, we show that the indicine ancestry of African cattle, although most closely related to so-far sampled North Indian indicine breeds, has a small amount of additional genetic affinity to Southeast Asian indicine breeds. Our findings support the hypothesis of aurochs introgression into African taurine and generate a novel hypothesis that the origin of indicine ancestry in Africa might be different indicine populations than the ones found in North India today.
Titanium particles in peri-implantitis: distribution, pathogenesis and prospects
Authors: Long Chen, Zian Tong, Hongke Luo, Yuan Qu, Xinhua Gu, Misi Si
Journal: International Journal of Oral Science (2023)

Abstract Peri-implantitis is one of the most important biological complications in the field of oral implantology. Identifying the causative factors of peri-implant inflammation and osteolysis is crucial for the disease’s prevention and treatment. The underlying risk factors and detailed pathogenesis of peri-implantitis remain to be elucidated. Titanium-based implants as the most widely used implant inevitably release titanium particles into the surrounding tissue. Notably, the concentration of titanium particles increases significantly at peri-implantitis sites, suggesting titanium particles as a potential risk factor for the condition. Previous studies have indicated that titanium particles can induce peripheral osteolysis and foster the development of aseptic osteoarthritis in orthopedic joint replacement. However, it remains unconfirmed whether this phenomenon also triggers inflammation and bone resorption in peri-implant tissues. This review summarizes the distribution of titanium particles around the implant, the potential roles in peri-implantitis and the prevalent prevention strategies, which expects to provide new directions for the study of the pathogenesis and treatment of peri-implantitis.
Multi-omics analysis reveals the molecular response to heat stress in a “red tide” dinoflagellate
Authors: Katherine E. Dougan, Zhi-Luo Deng, Lars Wöhlbrand, Carsten Reuse, Boyke Bunk, Yibi Chen, Juliane Hartlich, Karsten Hiller, Uwe John, Jana Kalvelage, Johannes Mansky, Meina Neumann-Schaal, Jörg Overmann, Jörn Petersen, Selene Sanchez-Garcia, Kerstin Schmidt-Hohagen, Sarah Shah, Cathrin Spröer, Helena Sztajer, Hui Wang, Debashish Bhattacharya, Ralf Rabus, Dieter Jahn, Cheong Xin Chan, Irene Wagner-Döbler
Journal: Genome biology (2023)

Abstract Background “Red tides” are harmful algal blooms caused by dinoflagellate microalgae that accumulate toxins lethal to other organisms, including humans via consumption of contaminated seafood. These algal blooms are driven by a combination of environmental factors including nutrient enrichment, particularly in warm waters, and are increasingly frequent. The molecular, regulatory, and evolutionary mechanisms that underlie the heat stress response in these harmful bloom-forming algal species remain little understood, due in part to the limited genomic resources from dinoflagellates, complicated by the large sizes of genomes, exhibiting features atypical of eukaryotes. Results We present the de novo assembled genome (~ 4.75 Gbp with 85,849 protein-coding genes), transcriptome, proteome, and metabolome from Prorocentrum cordatum , a globally abundant, bloom-forming dinoflagellate. Using axenic algal cultures, we study the molecular mechanisms that underpin the algal response to heat stress, which is relevant to current ocean warming trends. We present the first evidence of a complementary interplay between RNA editing and exon usage that regulates the expression and functional diversity of biomolecules, reflected by reduction in photosynthesis, central metabolism, and protein synthesis. These results reveal genomic signatures and post-transcriptional regulation for the first time in a pelagic dinoflagellate. Conclusions Our multi-omics analyses uncover the molecular response to heat stress in an important bloom-forming algal species, which is driven by complex gene structures in a large, high-G+C genome, combined with multi-level transcriptional regulation. The dynamics and interplay of molecular regulatory mechanisms may explain in part how dinoflagellates diversified to become some of the most ecologically successful organisms on Earth.
CREaTor: zero-shot cis-regulatory pattern modeling with attention mechanisms
Authors: Yongge Li, Fusong Ju, Zhiyuan Chen, Yiming Qu, Huanhuan Xia, Liang He, Lijun Wu, Jianwei Zhu, Bin Shao, Pan Deng
Journal: Genome biology (2023)

Abstract Linking cis -regulatory sequences to target genes has been a long-standing challenge. In this study, we introduce CREaTor, an attention-based deep neural network designed to model cis -regulatory patterns for genomic elements up to 2 Mb from target genes. Coupled with a training strategy that predicts gene expression from flanking candidate cis -regulatory elements (cCREs), CREaTor can model cell type-specific cis -regulatory patterns in new cell types without prior knowledge of cCRE-gene interactions or additional training. The zero-shot modeling capability, combined with the use of only RNA-seq and ChIP-seq data, allows for the ready generalization of CREaTor to a broad range of cell types.
Meta-Learned Models of Cognition
Authors: Marcel Binz, Ishita Dasgupta, Akshay K. Jagadish, Matthew Botvinick, Jane X. Wang, Eric Schulz
Journal: Behavioral and Brain Sciences (2023)

Psychologists and neuroscientists extensively rely on computational models for studying and analyzing the human mind. Traditionally, such computational models have been hand-designed by expert researchers. Two prominent examples are cognitive architectures and Bayesian models of cognition. While the former requires the specification of a fixed set of computational structures and a definition of how these structures interact with each other, the latter necessitates the commitment to a particular prior and a likelihood function which - in combination with Bayes' rule - determine the model's behavior. In recent years, a new framework has established itself as a promising tool for building models of human cognition: the framework of meta-learning. In contrast to the previously mentioned model classes, meta-learned models acquire their inductive biases from experience, i.e., by repeatedly interacting with an environment. However, a coherent research program around meta-learned models of cognition is still missing to this day. The purpose of this article is to synthesize previous work in this field and establish such a research program. We accomplish this by pointing out that meta-learning can be used to construct Bayes-optimal learning algorithms, allowing us to draw strong connections to the rational analysis of cognition. We then discuss several advantages of the meta-learning framework over traditional methods and reexamine prior work in the context of these new insights.
Seven days in medicine: 15-21 November 2023
Journal: BMJ (2023)

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Impact of treating obesity hypoventilation syndrome on body mass index
Authors: R.G.S. Andrade, J.F. Masa, J-C. Borel, L.F. Drager, P.R. Genta, B. Mokhlesi, G. Lorenzi-Filho
Journal: Pulmonology (2023)

To evaluate the impact of positive airway pressure (PAP) therapy on body mass index (BMI) in patients with obesity hypoventilation syndrome (OHS) associated with obstructive sleep apnea (OSA). Methods: A systematic review using the following terms: "obesity hypoventilation syndrome" AND "treatment" AND "randomized" using Cochrane Central Register of Controlled Trials, Medline and Web of Science was performed from the first data available until February 10, 2023. The inclusion criteria were: (1) original article; (2) adult OHS with concomitant OSA (apnea-hypopnea index or AHI ≥5 events/h); (3) randomized trial with PAP arm and standard care (control); (4) BMI evaluation at baseline and after the first months. We performed an individual participant data meta-analysis of randomized controlled trials. Our initial search retrieved 32 articles and 3 randomized studies fulfilled study criteria and were included in the final analysis, leading to a total of 342 participants. Patients were predominantly females (62%) and had OHS associated with at least mild OSA. As compared to baseline, a decrease in BMI was observed at study endpoint but this difference was not different intergroups (-0.50 ± 1.49 and -0.50 ±1.83, in control and PAP groups respectively (p=0.939)). Weight change was not associate with PAP adherence, OSA severity or use of supplemental oxygen. In contrast to treatment of eucapnic OSA with PAP that is associated with weight gain, treatment of OSA+OHS patients with or without PAP is associated with weight loss. Future studies are necessary to elucidate the mechanism by which weight loss occurs.
CDK5: an oncogene or an anti-oncogene: location location location
Authors: Kumar Nikhil, Kavita Shah
Journal: Molecular Cancer (2023)

Abstract Recent studies have uncovered various physiological functions of CDK5 in many nonneuronal tissues. Upregulation of CDK5 and/or its activator p35 in neurons promotes healthy neuronal functions, but their overexpression in nonneuronal tissues is causally linked to cancer of many origins. This review focuses on the molecular mechanisms by which CDK5 recruits diverse tissue-specific substrates to elicit distinct phenotypes in sixteen different human cancers. The emerging theme suggests that CDK5’s role as an oncogene or anti-oncogene depends upon its subcellular localization. CDK5 mostly acts as an oncogene, but in gastric cancer, it is a tumor suppressor due to its unique nuclear localization. This indicates that CDK5’s access to certain nuclear substrates converts it into an anti-oncogenic kinase. While acting as a bonafide oncogene, CDK5 also activates a few cancer-suppressive pathways in some cancers, presumably due to the mislocalization of nuclear substrates in the cytoplasm. Therefore, directing CDK5 to the nucleus or exporting tumor-suppressive nuclear substrates to the cytoplasm may be promising approaches to combat CDK5-induced oncogenicity, analogous to neurotoxicity triggered by nuclear CDK5. Furthermore, while p35 overexpression is oncogenic, hyperactivation of CDK5 by inducing p25 formation results in apoptosis, which could be exploited to selectively kill cancer cells by dialing up CDK5 activity, instead of inhibiting it. CDK5 thus acts as a molecular rheostat, with different activity levels eliciting distinct functional outcomes. Finally, as CDK5’s role is defined by its substrates, targeting them individually or in conjunction with CDK5 should create potentially valuable new clinical opportunities.
Hollow Cavity CaO<sub>2</sub>@Polydopamine Nanocomposites for pH‐Responsive Ca<sup>2+</sup>‐Enhanced Efficient Mild Hyperthermia in the NIR‐II Region
Authors: Yue Wang, Shuqi Wang, Shanshan Li, Wenyao Zhen, Xiaodan Jia, Xiue Jiang
Journal: Advanced Healthcare Materials (2023)

Abstract Second near‐infrared (NIR‐II) mild photothermal therapy with higher tissue penetration depth and less damage to healthy tissues is emerging as an attractive antitumor modality, but its therapeutic efficiency is dramatically suppressed by the resistance of heat shock proteins (HSPs). As a widely explored photothermal agent, the application of polydopamine (PDA) in the NIR‐II region is hampered by low photothermal conversion efficiency (PCE). Herein, its PCE in the NIR‐II region is improved by developing novel hollow cavity CaO 2 @PDA nanocomposites through chelation‐induced diffusion of inner core Ca 2+ to the shell PDA to facilitate multiple reflections of laser in the cavity. Upon pH‐responsive degradation of CaO 2 , its structure is transformed into a stacked “nano‐mesh” with excellent light absorption and an enlarged effective irradiation area. Overloading of Ca 2+ ions not only induces downregulation of HSPs but also enhances interference of light on membrane potential, which further aggravate mitochondrial dysfunction and reduce the thermotolerance of tumor cells, promoting efficient mild hyperthermia of PDA in the NIR‐II region.
Real-time machine learning model to predict in-hospital cardiac arrest using heart rate variability in ICU
Authors: Hyeonhoon Lee, Hyun-Lim Yang, Ho Geol Ryu, Chul-Woo Jung, Youn Joung Cho, Soo Bin Yoon, Hyun-Kyu Yoon, Hyung-Chul Lee
Journal: npj Digital Medicine (2023)

Predicting in-hospital cardiac arrest in patients admitted to an intensive care unit (ICU) allows prompt interventions to improve patient outcomes. We developed and validated a machine learning-based real-time model for in-hospital cardiac arrest predictions using electrocardiogram (ECG)-based heart rate variability (HRV) measures. The HRV measures, including time/frequency domains and nonlinear measures, were calculated from 5 min epochs of ECG signals from ICU patients. A light gradient boosting machine (LGBM) algorithm was used to develop the proposed model for predicting in-hospital cardiac arrest within 0.5-24 h. The LGBM model using 33 HRV measures achieved an area under the receiver operating characteristic curve of 0.881 (95% CI: 0.875-0.887) and an area under the precision-recall curve of 0.104 (95% CI: 0.093-0.116). The most important feature was the baseline width of the triangular interpolation of the RR interval histogram. As our model uses only ECG data, it can be easily applied in clinical practice.
Interpretable and intervenable ultrasonography-based machine learning models for pediatric appendicitis
Authors: Ričards Marcinkevičs, Patricia Reis Wolfertstetter, Ugne Klimiene, Kieran Chin-Cheong, Alyssia Paschke, Julia Zerres, Markus Denzinger, David Niederberger, Sven Wellmann, Ece Ozkan, Christian Knorr, Julia E. Vogt
Journal: Medical Image Analysis (2023)
Low-grade endotoxemia is associated with cardiovascular events in community-acquired pneumonia
Authors: Roberto Cangemi, Roberto Carnevale, Cristina Nocella, Camilla Calvieri, Simona Bartimoccia, Giacomo Frati, Pasquale Pignatelli, Vittorio Picchio, Francesco Violi
Journal: Journal of Infection (2023)

ObjectivesCommunity-acquired pneumonia (CAP) is associated with low-grade endotoxemia but its relationship with cardiovascular events (CVE) has not been investigated.MethodsWe evaluated the incidence of CVE including myocardial infarction, stroke, and cardiovascular death in 523 adult patients hospitalized for CAP. Serum lipopolysaccharide (LPS) and zonulin, a marker of gut permeability, were analyzed in the cohort, that was followed-up during hospitalization and up to 43 months thereafter.ResultsDuring the hospital-stay, 55 patients experienced CVE with a progressive increase from the lowest (0.6%) to highest LPS tertile (23.6%, p < 0.001). Logistic regression analyses showed that higher LPS tertile was independently associated with CVE; LPS significantly correlated with age, hs-CRP and zonulin. In a sub-group of 23 CAP patients, blood E. coli DNA was higher in patients compared to 24 controls and correlated with LPS. During the long-term follow-up, 102 new CVE were registered; the highest tertile of LPS levels was associated with incident CVE; Cox regression analysis showed that LPS tertiles, age, history of CHD, and diabetes independently predicted CVE.ConclusionsIn CAP low-grade endotoxemia is associated to short- and long-term risk of CVE. Further study is necessary to assess if lowering LPS by non-absorbable antibiotics may result in improved outcomes.
Asthma morbidity measures across Black ethnic subgroups
Authors: Leah Ishmael, Andrea Apter, Paula J. Busse, Rafael Calderon-Candelario, Jennifer K. Carroll, Thomas Casale, Juan C. Celedón, Rubin Cohen, Tamera Coyne-Beasley, Jing Cui, Brianna Ericson, Paulina Hernandez, David C. Kaelber, Nancy Maher, Conner Merriman, Giselle Mosnaim, Sylvette Nazario, Wanda Phipatanakul, Victor Pinto-Plata, Isaretta Riley, Kartik Shenoy, Juan Wisnivesky, Barbara Yawn, Elliot Israel, Juan Carlos Cardet
Journal: Journal of Allergy and Clinical Immunology (2023)
Re: Fred Saad, Noel W. Clarke, Mototsugu Oya, et al. Olaparib plus Abiraterone Versus Placebo plus Abiraterone in Metastatic Castration-resistant Prostate Cancer (PROpel): Final Prespecified Overall Survival Results of a Randomised, Double-blind, Phase 3 Trial. Lancet Oncol 2023;24:1094–108
Authors: Li Ding, Bin Yang, Xudong Yao
Journal: European Urology (2023)